tbuckley/cabot-search huggingface dataset:
Transcatheter mitral valve replacement or repair for secondary mitral regurgitation: a propensity score‐matched analysis
Authors: Sebastian Ludwig, Daniel Kalbacher, Walid Ben Ali, Jessica Weimann, Matti Adam, Alison Duncan, John G. Webb, Stephan Windecker, Mathias Orban, Cristina Giannini, Augustin Coisne, Nicole Karam, Andrea Scotti, Lars Sondergaard, Marianna Adamo, David W.M. Muller, Christian Butter, Paolo Denti, Bruno Melica, Damiano Regazzoli, Andrea Garatti, Tobias Schmidt, Martin Andreas, Gry Dahle, Maurizio Taramasso, Georg Nickenig, Nicolas Dumonteil, Thomas Walther, Michele Flagiello, Joerg Kempfert, Neil Fam, Hendrik Ruge, Tanja K. Rudolph, Moritz C. Wyler von Ballmoos, Marco Metra, Simon Redwood, Juan F. Granada, Gilbert H.L. Tang, Azeem Latib, Philipp Lurz, Ralph Stephan von Bardeleben, Thomas Modine, Jörg Hausleiter, Lenard Conradi
Journal: European Journal of Heart Failure (2023)

ABSTRACT Aims This study aimed to compare outcomes after transcatheter mitral valve replacement (TMVR) and mitral valve transcatheter edge‐to‐edge repair (M‐TEER) for the treatment of secondary mitral regurgitation (SMR). Methods and results The CHOICE‐MI registry included 262 patients with SMR treated with TMVR between 2014 and 2022. The EuroSMR registry included 1065 patients with SMR treated with M‐TEER between 2014 and 2019. Propensity score (PS) matching was performed for 12 demographic, clinical and echocardiographic parameters. Echocardiographic, functional and clinical outcomes out to 1 year were compared in the matched cohorts. After PS matching, 235 TMVR patients (75.5 years [70.0, 80.0], 60.2% male, EuroSCORE II 6.3% [interquartile range 3.8, 12.4]) were compared to 411 M‐TEER patients (76.7 years [70.1, 80.5], 59.0% male, EuroSCORE II 6.7% [3.9, 12.4]). All‐cause mortality was 6.8% after TMVR and 3.8% after M‐TEER at 30 days ( p = 0.11), and 25.8% after TMVR and 18.9% after M‐TEER at 1 year ( p = 0.056). No differences in mortality after 1 year were found between both groups in a 30‐day landmark analysis (TMVR: 20.4%, M‐TEER: 15.8%, p = 0.21). Compared to M‐TEER, TMVR resulted in more effective mitral regurgitation (MR) reduction (residual MR ≤1+ at discharge for TMVR vs. M‐TEER: 95.8% vs. 68.8%, p &lt; 0.001), and superior symptomatic improvement (New York Heart Association class ≤II at 1 year: 77.8% vs. 64.3%, p = 0.015). Conclusion In this PS‐matched comparison between TMVR and M‐TEER in patients with severe SMR, TMVR was associated with superior reduction of MR and superior symptomatic improvement. While post‐procedural mortality tended to be higher after TMVR, no significant differences in mortality were found beyond 30 days.
The next generation virus‐like particle platform for the treatment of peanut allergy
Authors: Jan M. Sobczak, Pascal S. Krenger, Federico Storni, Mona O. Mohsen, Ina Balke, Gunta Reseviča, Matthew D. Heath, Thalia L. Carreno Velazquez, Matthias F. Kramer, Callum J. W. Scott, Murray A. Skinner, Andris Zeltiņš, Thomas M. Kündig, Monique Vogel, Martin F. Bachmann
Journal: Allergy (2023)

Allergy to peanut is one of the leading causes of anaphylactic reactions among food allergic patients. Immunization against peanut allergy with a safe and protective vaccine holds a promise to induce durable protection against anaphylaxis caused by exposure to peanut. A novel vaccine candidate (VLP Peanut), based on virus-like particles (VLPs), is described here for the treatment of peanut allergy.VLP Peanut consists of two proteins: a capsid subunit derived from Cucumber mosaic virus engineered with a universal T-cell epitope (CuMVTT ) and a CuMVTT subunit fused with peanut allergen Ara h 2 (CuMVTT -Ara h 2), forming mosaic VLPs. Immunizations with VLP Peanut in both naïve and peanut-sensitized mice resulted in a significant anti-Ara h 2 IgG response. Local and systemic protection induced by VLP Peanut were established in mouse models for peanut allergy following prophylactic, therapeutic, and passive immunizations. Inhibition of FcγRIIb function resulted in a loss of protection, confirming the crucial role of the receptor in conferring cross protection against peanut allergens other than Ara h 2.VLP Peanut can be delivered to peanut-sensitized mice without triggering allergic reactions, while remaining highly immunogenic and offering protection against all peanut allergens. In addition, vaccination ablates allergic symptoms upon allergen challenge. Moreover, the prophylactic immunization setting conferred the protection against subsequent peanut-induced anaphylaxis, showing the potential for preventive vaccination. This highlights the effectiveness of VLP Peanut as a prospective break-through immunotherapy vaccine candidate toward peanut allergy. VLP Peanut has now entered clinical development with the study PROTECT.
Association of the gut microbiome with kidney function and damage in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL)
Authors: Brandilyn A. Peters, Qibin Qi, Mykhaylo Usyk, Martha L. Daviglus, Jianwen Cai, Nora Franceschini, James P. Lash, Marc D. Gellman, Bing Yu, Eric Boerwinkle, Rob Knight, Robert D. Burk, Robert C. Kaplan
Journal: Gut Microbes (2023)

Background The gut microbiome is altered in chronic kidney disease (CKD), potentially contributing to CKD progression and co-morbidities, but population-based studies of the gut microbiome across a wide range of kidney function and damage are lacking.Methods In the Hispanic Community Health Study/Study of Latinos, gut microbiome was assessed by shotgun sequencing of stool (n = 2,438; 292 with suspected CKD). We examined cross-sectional associations of estimated glomerular filtration rate (eGFR), urinary albumin:creatinine (UAC) ratio, and CKD with gut microbiome features. Kidney trait-related microbiome features were interrogated for correlation with serum metabolites (n = 700), and associations of microbiome-related serum metabolites with kidney trait progression were examined in a prospective analysis (n = 3,635).Results Higher eGFR was associated with overall gut microbiome composition, greater abundance of species from Prevotella, Faecalibacterium, Roseburia, and Eubacterium, and microbial functions related to synthesis of long-chain fatty acids and carbamoyl-phosphate. Higher UAC ratio and CKD were related to lower gut microbiome diversity and altered overall microbiome composition only in participants without diabetes. Microbiome features related to better kidney health were associated with many serum metabolites (e.g., higher indolepropionate, beta-cryptoxanthin; lower imidazole propionate, deoxycholic acids, p-cresol glucuronide). Imidazole propionate, deoxycholic acid metabolites, and p-cresol glucuronide were associated with prospective reductions in eGFR and/or increases in UAC ratio over ~6 y.Conclusions Kidney function is a significant correlate of the gut microbiome, while the relationship of kidney damage with the gut microbiome depends on diabetes status. Gut microbiome metabolites may contribute to CKD progression.
Nitrative Modification of Caveolin-3: A Novel Mechanism of Cardiac Insulin Resistance and a Potential Therapeutic Target Against Ischemic Heart Failure in Prediabetic Animals
Authors: Zhijun Meng, Zhen Zhang, Jianli Zhao, Caihong Liu, Peng Yao, Ling Zhang, Dina Xie, Wayne Bond Lau, Jumpei Tsukuda, Theodore A. Christopher, Bernard Lopez, Di Zhu, Demin Liu, John Ry Zhang, Erhe Gao, Harry Ischiropoulos, Walter Koch, Xinliang Ma, Yajing Wang
Journal: Circulation (2023)

Myocardial insulin resistance is a hallmark of diabetic cardiac injury. However, the underlying molecular mechanisms remain unclear. Recent studies demonstrate that the diabetic heart is resistant to other cardioprotective interventions, including adiponectin and preconditioning. The "universal" resistance to multiple therapeutic interventions suggests impairment of the requisite molecule(s) involved in broad prosurvival signaling cascades. Cav (Caveolin) is a scaffolding protein coordinating transmembrane signaling transduction. However, the role of Cav3 in diabetic impairment of cardiac protective signaling and diabetic ischemic heart failure is unknown.
Prognostic Value of Cutaneous Disease Severity Estimates on Survival Outcomes in Patients With Chronic Graft-vs-Host Disease
Authors: Emily Baumrin, Laura X. Baker, Michael Byrne, Paul J. Martin, Mary E. Flowers, Lynn Onstad, Najla El Jurdi, Heidi Chen, Alicia Beeghly-Fadiel, Stephanie J. Lee, Eric R. Tkaczyk
Journal: JAMA Dermatology (2023)

Prior studies have demonstrated an association between cutaneous chronic graft-vs-host disease (cGVHD) and mortality. Assessment of the prognostic value of different measures of disease severity would assist in risk stratification.
Human germline heterozygous gain-of-function<i>STAT6</i>variants cause severe allergic disease
Authors: Mehul Sharma, Daniel Leung, Mana Momenilandi, Lauren C.W. Jones, Lucia Pacillo, Alyssa E. James, Jill R. Murrell, Selket Delafontaine, Jesmeen Maimaris, Maryam Vaseghi-Shanjani, Kate L. Del Bel, Henry Y. Lu, Gilbert T. Chua, Silvia Di Cesare, Oriol Fornes, Zhongyi Liu, Gigliola Di Matteo, Maggie P. Fu, Donato Amodio, Issan Yee San Tam, Gavin Shueng Wai Chan, Ashish A. Sharma, Joshua Dalmann, Robin van der Lee, Géraldine Blanchard-Rohner, Susan Lin, Quentin Philippot, Phillip A. Richmond, Jessica J. Lee, Allison Matthews, Michael Seear, Alexandra K. Turvey, Rachael L. Philips, Terri F. Brown-Whitehorn, Christopher J. Gray, Kosuke Izumi, James R. Treat, Kathleen H. Wood, Justin Lack, Asya Khleborodova, Julie E. Niemela, Xingtian Yang, Rui Liang, Lin Kui, Christina Sze Man Wong, Grace Wing Kit Poon, Alexander Hoischen, Caspar I. van der Made, Jing Yang, Koon Wing Chan, Jaime Sou Da Rosa Duque, Pamela Pui Wah Lee, Marco Hok Kung Ho, Brian Hon Yin Chung, Huong Thi Minh Le, Wanling Yang, Pejman Rohani, Ali Fouladvand, Hassan Rokni-Zadeh, Majid Changi-Ashtiani, Mohammad Miryounesi, Anne Puel, Mohammad Shahrooei, Andrea Finocchi, Paolo Rossi, Beatrice Rivalta, Cristina Cifaldi, Antonio Novelli, Chiara Passarelli, Stefania Arasi, Dominique Bullens, Kate Sauer, Tania Claeys, Catherine M. Biggs, Emma C. Morris, Sergio D. Rosenzweig, John J. O’Shea, Wyeth W. Wasserman, H. Melanie Bedford, Clara D.M. van Karnebeek, Paolo Palma, Siobhan O. Burns, Isabelle Meyts, Jean-Laurent Casanova, Jonathan J. Lyons, Nima Parvaneh, Anh Thi Van Nguyen, Caterina Cancrini, Jennifer Heimall, Hanan Ahmed, Margaret L. McKinnon, Yu Lung Lau, Vivien Béziat, Stuart E. Turvey
Journal: The Journal of Experimental Medicine (2023)

STAT6 (signal transducer and activator of transcription 6) is a transcription factor that plays a central role in the pathophysiology of allergic inflammation. We have identified 16 patients from 10 families spanning three continents with a profound phenotype of early-life onset allergic immune dysregulation, widespread treatment-resistant atopic dermatitis, hypereosinophilia with esosinophilic gastrointestinal disease, asthma, elevated serum IgE, IgE-mediated food allergies, and anaphylaxis. The cases were either sporadic (seven kindreds) or followed an autosomal dominant inheritance pattern (three kindreds). All patients carried monoallelic rare variants in STAT6 and functional studies established their gain-of-function (GOF) phenotype with sustained STAT6 phosphorylation, increased STAT6 target gene expression, and TH2 skewing. Precision treatment with the anti–IL-4Rα antibody, dupilumab, was highly effective improving both clinical manifestations and immunological biomarkers. This study identifies heterozygous GOF variants in STAT6 as a novel autosomal dominant allergic disorder. We anticipate that our discovery of multiple kindreds with germline STAT6 GOF variants will facilitate the recognition of more affected individuals and the full definition of this new primary atopic disorder.
An Mpox-Related Death in the United States
Authors: Jemma Alarcón, Moon Kim, Dawn Terashita, Kusha Davar, Jacob M Garrigues, Jack P Guccione, Mark G Evans, Peera Hemarajata, Noah Wald-Dickler, Paul Holtom, Rodrigo Garcia Tome, Lovelyn Anyanwu, Naman K Shah, Matthew Miller, Todd Smith, Audrey Matheny, Whitni Davidson, Christina L Hutson, Jonathan Lucas, Odey C Ukpo, Nicole M Green, Sharon E Balter
Journal: New England Journal of Medicine (2023)
“Hairy Kidney” in Erdheim–Chester Disease
Authors: Nityasree Srialluri, Mohamed G Atta
Journal: New England Journal of Medicine (2023)

A 62-year-old man was incidentally found to have soft-tissue infiltration of the kidneys and severe hydronephrosis on CT. Histopathological examination of a core-biopsy specimen revealed pale-staining histiocytes.
p38MAPKα Stromal Reprogramming Sensitizes Metastatic Breast Cancer to Immunotherapy
Authors: Douglas V. Faget, Xianmin Luo, Matthew J. Inkman, Qihao Ren, Xinming Su, Kai Ding, Michael R. Waters, Ganesh Kumar Raut, Gaurav Pandey, Paarth B. Dodhiawala, Renata Ramalho-Oliveira, Jiayu Ye, Thomas Cole, Bhavna Murali, Alexander Zheleznyak, Monica Shokeen, Kurt R. Weiss, Joseph B. Monahan, Carl J. DeSelm, Adrian V. Lee, Steffi Oesterreich, Katherine N. Weilbaecher, Jin Zhang, David G. DeNardo, Sheila A. Stewart
Journal: Cancer Discovery (2023)

Metastatic breast cancer is an intractable disease that responds poorly to immunotherapy. We show that p38MAPKα inhibition (p38i) limits tumor growth by reprogramming the metastatic tumor microenvironment in a CD4+ T cell-, IFNγ-, and macrophage-dependent manner. To identify targets that further increased p38i efficacy, we utilized a stromal labeling approach and single-cell RNA sequencing. Thus, we combined p38i and an OX40 agonist that synergistically reduced metastatic growth and increased overall survival. Intriguingly, patients with a p38i metastatic stromal signature had better overall survival that was further improved by the presence of an increased mutational load, leading us to ask if our approach would be effective in antigenic breast cancer. The combination of p38i, anti-OX40, and cytotoxic T-cell engagement cured mice of metastatic disease and produced long-term immunologic memory. Our findings demonstrate that a detailed understanding of the stromal compartment can be used to design effective antimetastatic therapies. Immunotherapy is rarely effective in breast cancer. We dissected the metastatic tumor stroma, which revealed a novel therapeutic approach that targets the stromal p38MAPK pathway and creates an opportunity to unleash an immunologic response. Our work underscores the importance of understanding the tumor stromal compartment in therapeutic design. This article is highlighted in the In This Issue feature, p. 1275.
Acute and chronic impacts of heat stress on planetary health
Authors: Vanitha Sampath, Omar Shalakhti, Erika Veidis, Jo Ann Ifeoma Efobi, Mohamed H. Shamji, Ioana Agache, Chrysanthi Skevaki, Harald Renz, Kari C. Nadeau
Journal: Allergy (2023)

Abstract Heat waves are increasing in intensity, frequency, and duration causing significant heat stress in all living organisms. Heat stress has multiple negative effects on plants affecting photosynthesis, respiration, growth, development, and reproduction. It also impacts animals leading to physiological and behavioral alterations, such as reduced caloric intake, increased water intake, and decreased reproduction and growth. In humans, epidemiological studies have shown that heat waves are associated with increased morbidity and mortality. There are many biological effects of heat stress (structural changes, enzyme function disruption, damage through reactive oxygen or nitrogen species). While plants and animals can mitigate some of these effects through adaptive mechanisms such as the generation of heat shock proteins, antioxidants, stress granules, and others, these mechanisms may likely be inadequate with further global warming. This review summarizes the effects of heat stress on plants and animals and the adaptative mechanisms that have evolved to counteract this stress.
β3AR-Dependent Brain-Derived Neurotrophic Factor (BDNF) Generation Limits Chronic Postischemic Heart Failure
Authors: Alessandro Cannavo, Seungho Jun, Giuseppe Rengo, Federica Marzano, Jacopo Agrimi, Daniela Liccardo, Andrea Elia, Gizem Keceli, Giovanna G. Altobelli, Lorenzo Marcucci, Aram Megighian, Erhe Gao, Ning Feng, Kai Kammers, Nicola Ferrara, Livio Finos, Walter J. Koch, Nazareno Paolocci
Journal: Circulation Research (2023)

Loss of brain-derived neurotrophic factor (BDNF)/TrkB (tropomyosin kinase receptor B) signaling accounts for brain and cardiac disorders. In neurons, β-adrenergic receptor stimulation enhances local BDNF expression. It is unclear if this occurs in a pathophysiological relevant manner in the heart, especially in the β-adrenergic receptor-desensitized postischemic myocardium. Nor is it fully understood whether and how TrkB agonists counter chronic postischemic left ventricle (LV) decompensation, a significant unmet clinical milestone. We conducted in vitro studies using neonatal rat and adult murine cardiomyocytes, SH-SY5Y neuronal cells, and umbilical vein endothelial cells. We assessed myocardial ischemia (MI) impact in wild type, β3AR knockout, or myocyte-selective BDNF knockout (myoBDNF KO) mice in vivo (via coronary ligation [MI]) or in isolated hearts with global ischemia-reperfusion (I/R). In wild type hearts, BDNF levels rose early after MI (<24 hours), plummeting at 4 weeks when LV dysfunction, adrenergic denervation, and impaired angiogenesis ensued. The TrkB agonist, LM22A-4, countered all these adverse effects. Compared with wild type, isolated myoBDNF KO hearts displayed worse infarct size/LV dysfunction after I/R injury and modest benefits from LM22A-4. In vitro, LM22A-4 promoted neurite outgrowth and neovascularization, boosting myocyte function, effects reproduced by 7,8-dihydroxyflavone, a chemically unrelated TrkB agonist. Superfusing myocytes with the β3AR-agonist, BRL-37344, increased myocyte BDNF content, while β3AR signaling underscored BDNF generation/protection in post-MI hearts. Accordingly, the β1AR blocker, metoprolol, via upregulated β3ARs, improved chronic post-MI LV dysfunction, enriching the myocardium with BDNF. Last, BRL-37344-imparted benefits were nearly abolished in isolated I/R injured myoBDNF KO hearts. BDNF loss underscores chronic postischemic heart failure. TrkB agonists can improve ischemic LV dysfunction via replenished myocardial BDNF content. Direct cardiac β3AR stimulation, or β-blockers (via upregulated β3AR), is another BDNF-based means to fend off chronic postischemic heart failure.
Temperature Management after Cardiac Arrest — All In or Fold?
Authors: Stephen Bernard, Janet Bray
Journal: New England Journal of Medicine (2023)

Outcomes after out-of-hospital cardiac arrest have improved over the past 20 years; however, the benefits of some methods used to treat these patients remain uncertain. In particular, the body temperature to be targeted during the first 72 hours of care after an out-of-hospital cardiac arrest remains unclear despite multiple high-quality randomized trials having been conducted to investigate the issue.1-5 Early trials of therapeutic hypothermia targeted a body temperature of 32° to 34°C for 12 hours1 or 24 hours2 but without a specific target temperature in the control group. Subsequently, the Target Temperature Management 33°C versus 36°C after Out-of-Hospital Cardiac Arrest . . .
Predicting the Neurodevelopmental Outcome in Extremely Preterm Newborns Using a Multimodal Prognostic Model Including Brain Function Information
Authors: Laura Routier, Laurent Querne, Ghida Ghostine-Ramadan, Julie Boulesteix, Solène Graïc, Sandrine Mony, Fabrice Wallois, Emilie Bourel-Ponchel
Journal: JAMA Network Open (2023)

Early assessment of the prognosis of preterm newborns is crucial for accurately informing parents and making treatment decisions. The currently available prognostic models rarely incorporate functional brain information from conventional electroencephalography (cEEG).To examine the performance of a multimodal model combining (1) brain function information with (2) brain structure information (cranial ultrasonography), and (3) perinatal and (4) postnatal risk factors for the prediction of death or neurodevelopmental impairment (NDI) in extremely preterm infants.Preterm newborns (23-28 weeks' gestational age) admitted to the neonatal intensive care unit at Amiens-Picardie University Hospital were retrospectively included (January 1, 2013, to January 1, 2018). Risk factors from the 4 categories were collected during the first 2 weeks post delivery. Neurodevelopmental impairment was assessed at age 2 years with the Denver Developmental Screening Test II. No or moderate NDI was considered a favorable outcome. Death or severe NDI was considered an adverse outcome. Data analysis was performed from August 26, 2021, to March 31, 2022.After the selection of variables significantly associated with outcome, 4 unimodal prognostic models (considering each category of variable independently) and 1 multimodal model (considering all variables simultaneously) were developed. After a multivariate analysis for models built with several variables, decision-tree algorithms were run on each model. The areas under the curve for decision-tree classifications of adverse vs favorable outcomes were determined for each model, compared using bootstrap tests, and corrected for type I errors.A total of 109 newborns (58 [53.2% male]) born at a mean (SD) gestational age of 26.3 (1.1) weeks were included. Among them, 52 (47.7%) had a favorable outcome at age 2 years. The multimodal model area under the curve (91.7%; 95% CI, 86.4%-97.0%) was significantly higher than those of the unimodal models (P < .003): perinatal model (80.6%; 95% CI, 72.5%-88.7%), postnatal model (81.0%; 95% CI, 72.6%-89.4%), brain structure model (cranial ultrasonography) (76.6%; 95% CI, 67.8%-85.3%), and brain function model (cEEG) (78.8%; 95% CI, 69.9%-87.7%).In this prognostic study of preterm newborns, the inclusion of brain information in a multimodal model was associated with significant improvement in the outcome prediction, which may have resulted from the complementarity of the risk factors and reflected the complexity of the mechanisms that interfered with brain maturation and led to death or NDI.
Evaluation of Plasmapheresis vs Immunoglobulin as First Treatment After Ineffective Systemic Corticosteroid Therapy for Patients With Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis
Authors: Yuki Miyamoto, Hiroyuki Ohbe, Ryosuke Kumazawa, Hiroki Matsui, Kiyohide Fushimi, Hideo Yasunaga, Bon Ohta
Journal: JAMA Dermatology (2023)

Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) are severe cutaneous adverse reactions, and patients with SJS/TEN frequently require intensive care. However, there is limited evidence on the clinical outcomes of immunomodulating therapy, including plasmapheresis and intravenous immunoglobulin (IVIG) in patients with SJS/TEN.
Inequitable Exposures to U.S. Coal Power Plant–Related PM2.5: 22 Years and Counting
Authors: Lucas R.F. Henneman, Munshi Md Rasel, Christine Choirat, Susan C. Anenberg, Corwin Zigler
Journal: Environmental Health Perspectives (2023)

Emissions from coal power plants have decreased over recent decades due to regulations and economics affecting costs of providing electricity generated by coal vis-à-vis its alternatives. These changes have improved regional air quality, but questions remain about whether benefits have accrued equitably across population groups.
Pregnancy Complications and Long-Term Mortality in a Diverse Cohort
Authors: Stefanie N. Hinkle, Enrique F. Schisterman, Danping Liu, Anna Z. Pollack, Edwina H. Yeung, Sunni L. Mumford, Katherine L. Grantz, Yan Qiao, Neil J. Perkins, James L. Mills, Pauline Mendola, Cuilin Zhang
Journal: Circulation (2023)

Pregnancy complications are associated with increased risk of development of cardiometabolic diseases and earlier mortality. However, much of the previous research has been limited to White pregnant participants. We aimed to investigate pregnancy complications in association with total and cause-specific mortality in a racially diverse cohort and evaluate whether associations differ between Black and White pregnant participants.